4-Methylmorpholine → (S)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(2-(4-(heptyloxy)benzoyl)hydrazinecarbonyl)phenyl)propanoate

HRID 1775808Notes

Reaction equation

HRID 1775808 reaction equation
[C:1]([C:5]1[CH:28]=[CH:27][C:8]([C:9]([NH:11][C@H:12]([C:23]([O:25][CH3:26])=[O:24])[CH2:13][C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(Cl)(=O)OCC(C)C.[CH2:44]([O:51][C:52]1[CH:61]=[CH:60][C:55]([C:56]([NH:58][NH2:59])=[O:57])=[CH:54][CH:53]=1)[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50]>C1COCC1>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:9]([NH:11][C@@H:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([NH:59][NH:58][C:56](=[O:57])[C:55]3[CH:60]=[CH:61][C:52]([O:51][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])=[CH:53][CH:54]=3)=[O:19])=[CH:21][CH:22]=2)[C:23]([O:25][CH3:26])=[O:24])=[O:10])=[CH:27][CH:28]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 43737794-(Heptyloxy)benzohydrazideHCID 86689655(S)-4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoic acid

Product 1

HCID 86689659(S)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(2-(4-(heptyloxy)benzoyl)hydrazinecarbonyl)phenyl)propanoateYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of (S)-4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoic acid INT-1 (260 mg, 0.68 mmol) in THF (5 mL) were added 4-methylmorpholine (0.15 mL, 1.36 mmol) and isobutyl carbonochloridate (0.09 mL, 0.71 mmol). After stirring at room temperature for 2 h, 4-(heptyloxy)benzohydrazide (187 mg, 0.75 mmol) was added and stirring continued for another 2 h. The reaction mixture was poured onto NaHCO3 (50 mL) and extracted with DCM (3×20 mL). The combined organics were dried over MgSO4 and evaporated. The crude product was purified by column chromatography (100% EA in iso-hexanes) to afford 297 mg (71%) of (S)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(2-(4-(heptyloxy)benzoyl)hydrazinecarbonyl)phenyl)propanoate INT-3 as an off-white foam. LCMS-ESI (m/z) calculated for C36H45N3O6: 615.8 found 616.0 [M+H]+, tR=2.89 min. (Method 4).

Workup

  1. stirringstirring
  2. waitcontinued for another 2 h
  3. additionThe reaction mixture was poured onto NaHCO3 (50 mL)
  4. extractionextracted with DCM (3×20 mL)
  5. dry with materialThe combined organics were dried over MgSO4
  6. customevaporated
  7. customThe crude product was purified by column chromatography (100% EA in iso-hexanes)

Sources & evidence

ORD record
ord-28abf2ad5bad48429d8457abbe3e5053
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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